Triethylamine → cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide

HRID 853977노트

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HRID 853977 반응식
[NH2:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5].CCN(CC)CC.C[O:25][C:26](=O)[C:27]1[C:32]([NH:33][C:34]([CH:36]2[CH2:38][CH2:37]2)=[O:35])=[CH:31][CH:30]=[C:29]([Cl:39])[C:28]=1[CH2:40]Br>CN(C=O)C>[Cl:39][C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:34]([CH:36]2[CH2:37][CH2:38]2)=[O:35])=[C:27]2[C:28]=1[CH2:40][N:1]([CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:3][C:4]#[N:5])[C:26]2=[O:25]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 221771543-Amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrileHCID 669200082-Bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester

생성물 1

HCID 9981379cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide수율 80%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To the DMF solution (20 ml) of 3-Amino-3-(3-ethoxy-4-methoxy-phenyl)-propionitrile (1.55 g, 7 mmol) was added Et3N (1.6 ml, 12 mmol) followed by 2-bromomethyl-3-chloro-6-(cyclopropanecarbonyl-amino)-benzoic acid methyl ester (2.42 g, 7 mmol). The mixture was heated at 90° C. for 12 hrs then cooled to room temperature. The mixture was extracted with EtOAc (50 ml) and water (50 ml). The organic layer was washed with water (50 ml) and brine (50 ml), dried over Na2SO4 and concentrated in vacuo. The resulted oil was purified by silica gel chromatography to give cyclopropanecarboxylic acid {7-chloro-2-[2-cyano-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (2.4 g, 80%): mp 200-202° C.; 1H NMR (CDCl3)δ 0.90-0.94 (m, 2H, c-CH2), 1.09-1.14 (m, 2H, c-CH2), 1.45 (t, J=7.0 Hz, 3H, CH3), 1.64-1.70(m, 1H, c-CH), 3.12-3.32(m, 2H; CH2CN), 3.89(s, 3H), 3.99-4.12 (m, 3H, OCH2CH3+CHHN), 4.37 (d, J=18 Hz, 1H. CHHN), 5.62-5.68 (m, 1H, NCH), 6.87-6.98 (m, 3H, Ar), 7.40 (d, J=9 Hz, 1H, Ar), 8.47 (t, J=9 Hz, 1H, Ar), 10.34 (s, 1H, NH); 3C NMR (CDCl3) δ 8.5, 14.7, 16.2, 21.2, 46.4, 51.8, 56.0, 64.7, 111.7, 112.2, 116.9, 118.4, 119.1, 119.8, 121.9, 127.9, 133.3, 136.9, 138.9, 149.9, 150.0, 169.0, 172.7; Anal Calcd for C24H24ClN3O4: C, 63.50; H, 5.33; N, 9.26. Found: C, 63.43; H, 5.31; N, 9.01

후처리

  1. temperaturethen cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (50 ml) and water (50 ml)
  3. washThe organic layer was washed with water (50 ml) and brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulted oil was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-d1fc3d78f7d8433db8fcad028bea3024
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07256210B2

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